The liver plays a central and complex role in health, being responsible for synthesis of key molecules, maintenance of metabolic balance, and detoxification processes. Liver diseases are among the leading causes of death in the United States and their investigation spans basic science and clinical medicine. At the University of California, San Francisco, the liver is a major focus of study among scientists in fifteen Departments and two Schools (Medicine and Pharmacy) and is represented on three major campuses of the University (Moffitt-Long Hospital, San Francisco General Hospital, and the Veterans Affairs Medical Center). With the recent incorporation of Mt. Zion Medical Center among the UCSF campuses, it is anticipated that Center programs will eventually include investigators at that site as well. The Liver Center was established in 1975, assuming its current Core Center format in 1980, for the purposes of melding individual research programs into a consortium and of fostering interdisciplinary research through support of core facilities, funds for new initiatives, enrichment activities (including visiting scientists and mini-sabbatical programs), and the highly successful annual retreat. Center Core Facilities, among them Animals, Molecular Biology, Liver Cell Culture, Liver Perfusion, Microscopy, Biostatistics, and Mass Spectrometry, have provided important services to Center investigators during the present funding period. New research directions have emerged, and current areas of emphasis include basic and clinical studies in cell biology, drug metabolism and toxicity, hepatic fibrosis and cirrhosis, immunology and transplantation, metabolism, transport, bile secretion, and viral hepatitis. The research base has grown substantially, reflecting the favorable influences of several factors, including strong institutional commitment, continued successful operation of the liver transplantation program, and increasing interdisciplinary collaboration. Goals for the next funding period include further expansion of the use of molecular and genetic experimental approaches and the facilitation of clinical research, including the study of human materials. To this end, proposed major changes in core facilities include expansion of the Molecular Biology Core Facility, and establishment of a new Clinical and Biostatistics Core Facility. Dr. D.M. Bissell, currently a Center Associate Director, will assume the role of Co-Director. The Center enjoys the ongoing support of the leadership at UCSF, where it continues to be recognized for major contributions to digestive diseases research and serves as a national resource in providing rare animals or reagents and training in specialized techniques. It is anticipated that, during the next five years, the Center will facilitate increasing clinical and laboratory application of molecular approaches to address specific issues in human liver biology and disease, including studies of the pathogenesis of tumors and non-neoplastic disorders, development of diagnostic methods and reagents, and innovations in medical and surgical treatment.